Ketamine (Ketalor®, Ketaject®, Ketalar®) is a putative uncompetitive antagonist of calcium, sodium, and potassium transport through the N-methyl d-aspartate (NMDA) receptor. Ketamine binds at an allosteric site on the NDMA receptor. Ketamine is used to induce and maintain dissociative anesthesia and analgesia. Ketamine and other mechanistically similar agents, such as phencyclidine (PCP), amantadine, ibogaine, nitrous oxide, and dextromethorphan, are frequently co-administered with benzodiazepines (and triazolobenzodiazepines). Ketamine has a synergistic effect with opioids. Since many non-NMDA anesthetic agents modulate vascular tone, blood pressure, and respiration, their utility is governed by the presence and provision of artificial ventilation and cardiac function drugs. NMDA receptor antagonists do not suffer from this drawback. Ketamine induced effects are rapid, but they are short lived (Grant et al, British journal of Anaesthesiology 1983, 55, 1107-1111; Anderson et al, Biomedicine & Pharmacotherapy 2006, 60, 303-309; Clements et al, Journal of Pharmaceutical Sciences 1982, 71(5), 539-542; Hyjazi et al, British Journal of Anaesthesia 2003, 90(2), 155-160; Mazar et al, Anesthesiology 2005, 102, 1174-1181; Obach, Drug Metabolism and Disposition 1999, 27(11), 1350-1359; Persson et al, European Journal of Clinical Pharmacology 2002, 57, 869-875; White et al, British Journal of Anaesthesia 1985, 57, 197-203; Yanagihara et al, Biopharmaceutics & Drug Disposition 2003, 24, 37-43.

The half-life of ketamine can range from about two to about five hours, depending on the mode of administration. Nasal administration of Ketamine not only increases Ketamine's half life, but also provides a higher bioavailability than other forms of administration, with F ranging from approximately 20% to 50%. Ketamine affords a blood to plasma ratio of ˜0.82 and readily crosses the blood brain barrier. Ketamine has two enantiomers, each with unique characteristics. The S-(+) isomer is approximately four times more potent than the R-(−) isomer. Each enantiomer has a similar half-life. The S-(+) isomer is reported to be superior in inducing anesthesia, leads to a faster recovery, and has a lower incidence of emergence delirium. S-(+) isomer administration, however, causes more overall side-effects, but the side-effects are considered minor. Ketamine's role in neuroprotection and neurodegradation is ambiguous. Acute ketamine use can provide neuroprotection by increasing cerebral blood flow, thereby hindering cerebral ischemia progression, and by maintaining normal cardiac parameters during administration. On the other hand, long-term ketamine use causes vacuole formation in animals, which has been linked to neurodegration. It is not clear, however, whether vacuole formation results from the action of the parent drug itself or from the action of one of its metabolites. Ketamine is subject to extensive first-pass metabolism, mainly through oxidation catalyzed by CYP3A4. A primary metabolite of Ketamine is N-desmethylketamine, usually referred to as “norketamine.” Norketamine is roughly one third as potent as the parent drug and has a half-life of about five hours. Another detected metabolite, dehydronorketamine, may be a contaminant as opposed to an actual in vivo metabolite. Much of the excreted material consists of glucuronidated and hydroxylated material.